A Bis(Acridino)-Crown Ether for Recognizing Oligoamines in Spermine Biosynthesis.

Oligoamines in cellular metabolism carry extremely diverse biological functions (i.e., regulating Ca2+-influx, neuronal nitric oxide synthase, membrane potential, Na+, K+-ATPase activity in synaptosomes, etc.). Furthermore, they also act as longevity agents and have a determinative role in autophagy, cell growth, proliferation, and death, while oligoamines dysregulation is a key in a variety of cancers. However, many of their mechanisms of actions have just begun to be understood. In addition to the numerous biosensing methods, only a very few simple small molecule-based tests are available for their selective but reversible tracking or fluorescent labeling. Motivated by this, we present herein a new fluorescent bis(acridino)-crown ether as a sensor molecule for biogenic oligoamines. The sensor molecule can selectively distinguish oligoamines from aliphatic mono- and diamino-analogues, while showing a reversible 1:2 (host:guest) complexation with a stepwise binding process accompanied by a turn-on fluorescence response. Both computational simulations on molecular docking and regression methods on titration experiments were carried out to reveal the oligoamine-recognition properties of the sensor molecule. The new fluorescent chemosensor molecule has a high potential for molecular-level functional studies on the oligoamine systems in cell processes (cellular uptake, transport, progression in cancers, etc.).

Ultrafast Solid-Phase Oxidation of Aldehydes to Carboxylic Acids by Atmosphseric Plasma Treatment.

Although atmospheric plasma treatment is an industrially widespread, scalable, and environmentally friendly method, it has been generally used for surface modification, decontamination, or sterilization. In this paper, a novel, sustainable, green, and ultrafast oxidation method is described for aldehydes on a preparative thin-layer chromatographic plate as a solid support. The plasma treatment has proven to be suitable for producing the corresponding carboxylic acids by using only air as a reactant source under mild reaction conditions, while the isolation of the products is also directly integrated into the oxidation process. Extensibility to other reaction types is not explored yet, but we are sure that this novel synthesis conception carries a lot of possibilities.

Covalently Modified Molecular-Recognition-Capable UV-Transparent Microplate for Ultra-High-Throughput Screening of Dissolved Zn2+ and Pb2.

Zn2+ has a crucial role both in biology and the environment, while Pb2+ presents serious hazards in the same areas due to its toxicity, and the need for their analysis often exceeds available instrumental capacity. We report, herein, a new high-throughput optochemical screening method for Zn2+ and Pb2+ in various solutions. Moreover, we also introduced a new and generalizable three-step-microplate-modification technique, including plasma treating, linker-docking and photocatalytic copolymerization. The surface of a commercially available 96-well-cycloolefin-microplate was treated with atmospheric plasma, and then, the bottoms of the wells were covered by covalently attaching a methacrylate-containing linker-monolayer. Finally, the preactivated microplate wells were covalently functionalized by immobilizing bis(acridino)-crown ether-type sensor molecules, via photocatalytic copolymerization, to a polymethacrylate backbone. This sensing tool can be used in all microplate readers, is compatible with liquid handling platforms and provides an unprecedently fast monitoring (>1000 samples/hour, extrapolated from the time required for 96 measurements) of dissolved Zn2+ and Pb2+ among recent alternatives above the detection limits of 8.0 × 10-9 and 3.0 × 10-8 mol/L, respectively, while requiring a sample volume of only 20 µL.

Cariprazine maintenance treatment during pregnancy - a case report.

Data on reproductive safety of recently approved newer antipsychotics are limited. Here, we report a case vignette of a patient with schizophrenia treated with cariprazine during pregnancy. The patient became pregnant unexpectedly while taking medication. As a result of shared decision-making, the patient and her psychiatrist decided to continue the treatment, which proved to be protective against relapse and had no adverse effect either on the course of pregnancy or on the health of the newborn. Cariprazine maintenance treatment during pregnancy was found to be safe in our case.

Synthetic Modifications of a Pb2+-Sensor Acridono-Crown Ether for Covalent Attachment and Their Effects on Selectivity.

Because of environmental impact, there is a great need for chemosensors, especially for toxic heavy metals such as lead. The conventional instrumental analytical techniques rarely provide an available real-time sensing platform, thus the development of highly selective and stable synthetic chemosensor molecules is of great importance. Acridono-18-crown-6 ethers have such properties, and much research has proven their outstanding applicability in various supramolecular devices. In this present work, we aimed to enable their covalent immobilization capability by synthesizing functionalized derivatives while preserving the favored molecular recognition ability. Several new macrocycle analogues were synthesized, while synthetization difficulties and design aspects were also dealt with. The selectivity of the macrocycle analogues was studied using UV-Vis spectroscopy and compared with that of the parent compounds. The ultimate crown ether derivative showed high Pb2+-selectivity, reversibility (decomplexation by extraction with water) and stability.

Investigation of peripheral inflammatory biomarkers in association with suicide risk in major depressive disorder.

Suicide is the most severe complication of major depressive disorder (MDD). Novel research assumes the role of immunological dysregulation in the background - several studies have reported alterations in the number of inflammatory cells related to both MDD and suicidality. There are currently no objective, routinely measured parameters to indicate suicidal vulnerability. However, altered inflammatory cell numbers and ratios have been proposed as potential biomarkers of suicide risk (SR). The present research aims to examine changes of these values related to increased SR in MDD as an assumed inflammatory state. We investigated laboratory parameters of psychiatric in-patients diagnosed with MDD (n = 101) retrospectively. Individuals with recent suicide attempt (SA) (n = 22) and with past SA (n = 19) represented the high SR group. MDD patients with no history of SA (n = 60) composed the intermediate SR group. We compared the number of neutrophil granulocytes, monocytes, lymphocytes, platelets, white blood cell count (WBC), neutrophil-to-lymphocyte (NLR), monocyte-to-lymphocyte (MLR), platelet-to-lymphocyte ratio (PLR), mean platelet volume (MPV), red blood cell distribution width (RDW) and erythrocyte sedimentation rate (ESR). Furthermore, we evaluated alterations of these parameters related to antidepressant (AD) and antipsychotic (AP) treatment, which have been proved to have anti-inflammatory effects. We found a significant increase in neutrophil granulocyte count, NLR, monocyte count, MLR, WBC and ESR in patients with recent SA compared to patients with no history of SA. Moreover, there was a significant elevation in monocyte count, MLR, ESR and RDW in patients with high SR compared to patients with intermediate SR. AD treatment resulted in a significant decrease in neutrophil granulocyte count and NLR, however, it did not affect monocyte count and MLR. Assuming immunological mechanisms in the background of MDD and suicidality, our findings support the role of NLR as a biomarker of acute SR, though its alterations may be masked by possible anti-inflammatory effects of AD treatment in the long term. However, MLR, a marker exhibiting changes which are not attenuated by pharmacotherapy, may be a possible indicator of both acute and long-term suicidal vulnerability.

Enhancing biophotovoltaic efficiency: Study on a highly productive green algal strain Parachlorella kessleri MACC-38.

Biophotovoltaic (BPV) devices are a potential decentralized and environmentally friendly energy source that harness solar energy through photosynthesis. BPV devices are self-regenerating, promising long-term usability. A practical strategy for enhancing BPV performance is to systematically screen for highly exoelectrogenic algal strains capable of generating large electric current density. In this study, a previously uncharacterized green algal strain - Parachlorella kessleri MACC-38 was found to generate over 340 µA mg-1 Chl cm-2. This output is approximately ten-fold higher than those of Chlamydomonas reinhardtii and Chlorella species. The current production of MACC-38 primarily originates from photosynthesis, and the strain maintains its physiological integrity throughout the process. MACC-38 exhibits unique traits such as low extracellular O2 and Fe(III) reduction, substantial copper (II) reduction, and significant extracellular acidification during current generation, contributing to its high productivity. The exoelectrogenic and growth characteristics of MACC-38 suggest that it could markedly boost BPV efficiency.

Roots Fuel Cell Produces and Stores Clean Energy.

In recent years, extensive scientific efforts have been conducted to develop clean bioenergy technologies. A promising approach that has been under development for more than a hundred years is the microbial fuel cell (MFC) which utilizes exoelectrogenic bacteria as an electron source in a bioelectrochemical cell. The viability of bacteria in soil MFCs can be maintained by integrating plant roots, which release organic materials that feed the bacteria. In this work, we show that rather than organic compounds, roots also release redox species that can produce electricity in a biofuel cell. We first studied the reduction of the electron acceptor Cytochrome C by green onion roots. We integrate green onion roots into a biofuel cell to produce a continuous bias-free electric current for more than 24 h in the dark. This current is enhanced upon irradiation of the onion's leaves with light. We apply cyclic voltammetry and 2D-fluorescence measurements to show that NADH and NADPH act as major electron mediators between the roots and the anode, while their concentrations in the external root matrix are increased upon irradiation of the leaves. Finally, we show that roots can contribute to energy storage by charging a supercapacitor.

Diagnostic and Prognostic Value of PACAP in Multiple Myeloma.

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a multifunctional neuropeptide with well-known anti-inflammatory, antioxidant, antitumor, and immunomodulatory effects. PACAP regulates the production of various proinflammatory factors and may influence the complex cytokine network of the bone marrow microenvironment altered by plasma cells, affecting the progression of multiple myeloma (MM) and the development of end-organ damage. The aim of our study was to investigate the changes in PACAP-38 levels in patients with MM to explore its value as a potential biomarker in this disease. We compared the plasma PACAP-38 levels of MM patients with healthy individuals by ELISA method and examined its relationship with various MM-related clinical and laboratory parameters. Lower PACAP-38 levels were measured in MM patients compared with the healthy controls, however, this difference vanished if the patient achieved any response better than partial response. In addition, lower peptide levels were found in elderly patients. Significantly higher PACAP-38 levels were seen in patients with lower stage, lower plasma cell infiltration in bone marrow, lower markers of tumor burden in serum, lower total urinary and Bence-Jones protein levels, and in patients after lenalidomide therapy. Higher PACAP-38 levels in newly diagnosed MM patients predicted longer survival and a higher probability of complete response to treatment. Our findings confirm the hypothesis that PACAP plays an important role in the pathomechanism of MM. Furthermore, our results suggest that PACAP might be used as a valuable, non-invasive, complementary biomarker in diagnosis, and may be utilized for prognosis prediction and response monitoring.

Enantiodiscriminating Lipophilic Liquid Membrane-Based Assay for High-Throughput Nanomolar Enantioenrichment of Chiral Building Blocks.

The reported optical resolution method was designed to support high-throughput enantioseparation of molecular building blocks obtained by automated small-scale synthetic methods. Lipophilic esters of common resolving agents were prepared and used as liquid membranes on the indifferent polymer surface of a microtiter assay. Chiral model compounds were enriched in one of the enantiomers starting from the aqueous solutions of their racemic mixture. Enantiodiscrimination was provided by forming diastereomeric coordination complexes of lipophilic enantiopure esters with the enantiomers of the chiral building blocks inside the liquid membranes. This enantiomeric recognition resulted in a greater distribution ratio of the preferred isomer in the membrane phase, thus the process enables a simultaneous enantioenrichment of the solutions outside the membrane. This paper reports a novel microplate-integrated stereoselective membrane enrichment technique satisfying the need for automatable enantioseparation on a subpreparative scale.

Comparison of Length of Hospital Stay for Community-Acquired Infections Due to Enteric Pathogens, Influenza Viruses and Multidrug-Resistant Bacteria: A Cross-Sectional Study in Hungary.

Community-acquired infections (CAI) can affect the duration of care and mortality of patients. Therefore, we aimed to investigate these as well as factors influencing the length of hospital stay in patients with CAI due to enteric pathogens, influenza viruses and multidrug-resistant (MDR) bacteria. We obtained data on 531 patients with CAI from the medical databases of a Hungarian university hospital and analyzed their characteristics using a regression model. Patients with MDR bacterial infection had the highest mortality (26.24%) and they stayed significantly longer in the hospital than cases with other CAIs. Our results showed that infection by Clostridioides difficile (odds ratio (OR): 6.98, 95% confidence interval (CI): 1.03-47.48; p = 0.047), MDR Escherichia coli (OR: 7.64, 95% CI: 1.24-47.17; p = 0.029), MDR Klebsiella spp. (OR: 7.35, 95% CI: 1.15-47.07; p = 0.035) and hospitalization in the department of pulmonology (OR: 5.48, 95% CI: 1.38-21.76; p = 0.016) and surgery (OR: 4.19, 95% CI: 1.18-14.81; p = 0.026) significantly increased, whereas female sex (OR: 0.62, 95% CI: 0.40-0.97; p = 0.037) and hospitalization in the department of pediatrics (OR: 0.17, 95% CI: 0.04-0.64; p = 0.009) decreased the odds of staying in the hospital for more than 6 days. Our findings provide new information on the epidemiology of CAI and can contribute to the development of public health programs that decrease the burden of infections acquired in the community.

Covalently Immobilizable Tris(Pyridino)-Crown Ether for Separation of Amines Based on Their Degree of Substitution.

A great number of biologically active compounds contain at least one amine function. Appropriate selectivity can only be accomplished in a few cases upon the substitution of these groups, thus functionalization of amines generally results in a mixture of them. The separation of these derivatives with very similar characteristics can only be performed on a preparative scale or by applying pre-optimized HPLC methods. A tris(pyridino)-crown ether was designed and synthetized for overcoming these limitations at a molecular level. It is demonstrated, that this selector molecule is able to distinguish protonated primary, secondary and tertiary amines by the formation of reversible complexes with different stabilities. This degree of substitution-specific molecular recognition of amines opens the door to develop separation processes primarily focusing on the purification of biologically active compounds in a nanomolar scale.

A cuvette-compatible Zn2+ sensing tool for conventional spectrofluorometers prepared by copolymerization of macrocyclic fluoroionophores on quartz glass surface.

We report here the development of a surface-modified quartz glass sheet, which affords an opportunity for converting conventional spectrofluorometers to ion-selective optochemical sensors by placing it diagonally into a photometric cuvette. Moreover, we describe a generalizable technique, which allows the usage of any polymerizable ionophores for developing multiple-use fluorescent chemosensors of various selectivity. A fluorescent bis(acridino)-crown ether containing allyl groups was photocatalytically copolymerized with a methacrylate-acrylamide-based monomer mixture to obtain an ion-selective sensor membrane layer on the surface of the cuvette-compatible glass sheet. This glass membrane-based direct optode enabled the analysis of Zn2+above a lower limit of detection of 2.2 × 10-7mol·l-1with an excellent reusability. Limiting factors, like pH and competing ionic or organic agents were thoroughly investigated. Moreover, spiked river-water samples were measured to demonstrate applicability. The proposed sensor placed in any conventional spectrofluorometer provides an innovative method for perturbation-free analysis of Zn2+for all the chemists in need of a fast, easy-to-use, portable and regenerable analyzer without the requirement of an analyte-specific instrumentation.

PACAP-38 and PAC1 Receptor Alterations in Plasma and Cardiac Tissue Samples of Heart Failure Patients.

Pituitary adenylate cyclase activating polypeptide-38 (PACAP-38) is a multifunctional neuropeptide, which may play a role in cardioprotection. However, little is known about the presence of PACAP-38 in heart failure (HF) patients. The aim of our study was to measure the alterations of PACAP-38 like immunoreactivity (LI) in acute (n = 13) and chronic HF (n = 33) and to examine potential correlations between PACAP-38 and HF predictors (cytokines, NT-proBNP). Tissue PACAP-38 LI and PAC1 receptor levels were also investigated in heart tissue samples of patients with HF. Significantly higher plasma PACAP-38 LI was detected in patients with acute HF, while in chronic HF patients, a lower level of immunoreactivity was observed compared to healthy controls (n = 13). Strong negative correlation was identified between plasma PACAP-38 and NT-proBNP levels in chronic HF, as opposed to the positive connection seen in the acute HF group. Plasma IL-1 ß, IL-2 and IL-4 levels were significantly lower in chronic HF, and IL-10 was significantly higher in patients with acute HF. PACAP-38 levels of myocardial tissues were lower in all end-stage HF patients and lower PAC1 receptor levels were detected in the primary dilated cardiomyopathy group compared to the controls. We conclude that PACAP-38 and PAC1 expression correlates with some biomarkers of acute and chronic HF; therefore, further studies are necessary to explore whether PACAP could be a suitable prognostic biomarker in HF patients.

Examination of pituitary adenylate cyclase-activating polypeptide in Parkinson's disease focusing on correlations with motor symptoms.

The neuroprotective effects of pituitary adenylate cyclase-activating polypeptide (PACAP) have been shown in numerous in vitro and in vivo models of Parkinson's disease (PD) supporting the theory that PACAP could have an important role in the pathomechanism of the disorder affecting mostly older patients. Earlier studies found changes in PACAP levels in neurological disorders; therefore, the aim of our study was to examine PACAP in plasma samples of PD patients. Peptide levels were measured with ELISA and correlated with clinical parameters, age, stage of the disorder based on the Hoehn and Yahr (HY) scale, subtype of the disease, treatment, and specific scores measuring motor and non-motor symptoms, such as movement disorder society-unified Parkinson's disease rating scale (MDS-UPDRS), Epworth sleepiness scale (ESS), Parkinson's disease sleep scale (PDSS-2), and Beck depression inventory (BDI). Our results showed significantly decreased PACAP levels in PD patients without deep brain stimulation (DBS) therapy and in akinetic-rigid subtype; additionally we also observed a further decrease in the HY stage 3 and 4. Elevated PACAP levels were found in patients with DBS. There were no significant correlations between PACAP level with MDS-UPDRS, type of pharmacological treatment, PDSS-2 sleepiness, or depression (BDI) scales, but we found increased PACAP level in patients with more severe sleepiness problems based on the ESS scale. Based on these results, we suggest that following the alterations of PACAP with other frequently used clinical biomarkers in PD patients might improve strategic planning of further therapeutic interventions and help to provide a clearer prognosis regarding the future perspective of the disease.

Evaluation of advanced oxidation processes for ß-blockers degradation: a review.

This study summarizes the results of scientific investigations on the removal of the three most often used ß-blockers (atenolol, metoprolol and propranolol) by various advanced oxidation processes (AOP). The free radical chemistry, rate constants, degradation mechanism and elimination effectiveness of these compounds are discussed together with the technical details of experiments. In most AOP the degradation is predominantly initiated by hydroxyl radicals. In sulfate radical anion-based oxidation processes (SROP) both hydroxyl radicals and sulfate radical anions greatly contribute to the degradation. The rate constants of reactions with these two radicals are in the 109-1010 M-1 s-1 range. The degradation products reflect ipso attack, hydroxylation on the aromatic ring and/or the amino moiety and cleavage of the side chain. Among AOP, photocatalysis and SROP are the most effective for degradation of the three ß-blockers. The operating parameters have to be optimized to the most suitable effectiveness.

Bioelectricity generation from live marine photosynthetic macroalgae.

The conversion of solar energy into electrical current by photosynthetic organisms has the potential to produce clean energy. Bio-photoelectrochemical cells (BPECs) utilizing unicellular photosynthetic microorganisms have been studied, however similar harvesting of electrons from more evolved intact photosynthetic organisms has not been previously reported. In this study, we describe for the first time BPECs containing intact live marine macroalgae (seaweeds) in natural seawater or saline buffer. The BPECs produce electrical currents of >50 mA/cm2, from both light-dependent (photosynthesis) and light-independent processes. These values are significantly greater than the current densities that have been reported for single-cell microorganisms. The photocurrent is inhibited by the Photosystem II inhibitor 3-(3,4-dichlorophenyl)-1,1-dimethylurea, indicating that the source of light-driven electrons is from photosynthetic water oxidation. The current is mediated to the external anode via NADPH and possibly other reduced molecules. We show that intact macroalgae cultures can be used in large-scale BPECs containing seawater, to produce bias-free photocurrents, paving the way for the future development of low-cost energy solar energy conversion technologies using BPECs.

Elimination of oxacillin, its toxicity and antibacterial activity by using ionizing radiation.

The chemical changes caused by electron beam and γ irradiations and the biochemical characteristics of degradation products of a frequently used antibiotic oxacillin were investigated and compared with those of cloxacillin by applying pulse radiolysis, chemical and biochemical oxygen demand, total organic carbon content, oxygen uptake rate, toxicity and antibacterial activity measurements. Oxacillin was found to be non-toxic, but poorly biodegradable by the mixed microbial population of the activated sludge of a wastewater treatment plant. Therefore, it can significantly contribute to the spread of ß-lactam antibiotic resistant bacteria. However, the products formed by γ-irradiation were more easily biodegradable as they were utilized as nutrient source by the microbes of the activated sludge and the products did not show antibacterial activity. During irradiation treatment of aerated aqueous solutions mainly hydroxyl radicals induce the elimination of antimicrobial activity by making alterations at the bicyclic ß-lactam part of these antibiotics. Since the ß-lactam part is the same in oxacillin and cloxacillin, the biochemical characteristics of products of the two antibiotics are similar. The attack of hydrated electron takes place on the carbonyl groups. When the irradiation is made under anoxic conditions these reactions may also contribute considerably to alterations at the ß-lactam part and thereby to the loss of antibacterial activity.

New Polymerizable Tetraaza Macrocycle Containing Two Acridine Units for Selective Fluorescence Sensing of Metal Ions.

A new fluorescent bis(acridino)-macrocycle containing two allyl groups was synthesized and photophysically studied. Studies were carried out on metal ion recognition and selectivity-influencing effects including the determination of the relevant thermodynamic constants as logK and pKa. The proposed sensor molecule is recommended for the development of Zn2+-selective optochemical analyzers based on covalently immobilized ionophores as it has a unique pH-independent metal ion recognition ability, which is not influenced by anions and other potentially occurring metal ions in biological samples.